Fever pitch: Globavir says dengue effort could work in Ebola, both early stage

By Randy Osborne Staff Writer

Globavir Biosciences Inc. formally threw its hat into the Ebola ring, making known the firm's plan to develop the preclinical candidate GBV006 as a potential remedy for the virulent outbreak in West Africa.

Shalabh Gupta, CEO of Los Altos, Calif.-based Globavir, said the firm was working on Ebola "way before it became such a big deal." Research has been under way for the past 10 months or so. "When I say we were working on Ebola, I mean we were pursuing hemorrhagic fevers," he said. "We waited until we had some data, and to see how the rest of the world was shaping up." GBV006 is described as a combination of FDA-approved therapies that Gupta declined to disclose.

Discovery of GBV006's worth in infectious diseases was made at Stanford University School of Medicine, and Globavir holds the worldwide exclusive license to develop and market the compound, which is said to target several stages of the virus' life cycle.

Globavir also is pursuing a candidate for dengue fever. That illness and Ebola "have good homology specifically when it comes down to the genome," Gupta said. "They're not in the same family of viruses, but there are at least two mechanisms that are important. One is viral entry into the cells and the other is viral replication within the cells." Globavir's approach "make[s] it easier or even possible" for a therapy to work in more than one capacity, and "something that works in dengue can have potential applications in Ebola."

The dengue program has more advanced animal data than the push in Ebola, and Globavir plans to talk with FDA at the end of this year or the start of next year with regard to a dengue candidate, and file an investigational new drug application in early 2015.

Among its three diagnostic tests, Globavir has one for dengue, and aims to have a companion diagnostic included on the label of the dengue treatment, if approved. "In this regard, our approach is quite different," Gupta said. "We do not want to give our drug to every single patient out there. We believe we can quantify the viral load, and we want to go after patients who have very high viral loads," since they are the most serious.

"Animal trials are [still] ongoing" in the Ebola research, Gupta told BioWorld Today. "The challenge lies [in knowing at] what level do you have enough data to go into humans. In dengue, the mortality is not that high," and in Ebola the demand is great.

"I'm very concerned about the problem," Gupta said. "We have not [reached] the point that we would go to the FDA yet. This doesn't mean we will not go to the FDA, but we are also contemplating regulatory pathways outside the U.S. It's a global problem." He said he would have a better idea about the Ebola strategy "in the next six weeks or so."

'THE NEXT LOGICAL STEP'

With a therapy that combines familiar drugs, "whatever their safety issues are, at least we know, in hundreds of thousands of patients," Gupta pointed out. "We know how to use those drugs. What is unknown about them is efficacy." Globavir has already seen its thesis "playing out very well in dengue treatment in advanced animal models," he added.

The dengue drug in development is not the same as the potential Ebola therapy, "not at the moment," Gupta said. "We will be able to figure that out [later], but we're evaluating more than one drug combination in Ebola. Obviously, we have one particular combination, which is the product that we think is most advanced" in dengue.

Globavir's platform technology deploys computational algorithms to find chemical and structural features necessary for a drug's therapeutic activity, identifying the players most likely to succeed from the firm's in-house database of nontoxic and physiological active compounds, Gupta said.

"Instead of designing new chemical entities, which we can use this platform for, we have decided to use existing databases of drugs and other naturally occurring products," he said. "We can computationally predict their efficacy based on the data we have. The traditional drug model, if you will, was looking at two-dimensional interactions between a drug and its target. Our platform is three-dimensional, so if there is more than one target the drug is interacting with, we can look at those targets and be able to predict a potential efficacy profile as well as side effects."

Gupta founded Mountain View, Calif.-based Biocycive Inc. in late 2010, focused on small-molecule drugs and based on technology from Stanford as well as the University of Southern California. Globavir started in 2013, and Biocycive since has become a wholly owned subsidiary. With six employees and "a bunch of consultants," Globavir also has an office in Halifax, Nova Scotia.

About collaborators in the dengue and Ebola efforts, Gupta said his firm is "not actively searching, but there has been interest from pharma. We want to take the program to the logical next step. Whether we do it on our own or with a partner is open to discussion."

Ultimately, the company will need global commercialization help. In the meantime, "if we don't find the right partner, we're willing to wait," he said.